Increased Incidence of Barotrauma in Patients with COVID-19 on Invasive Mechanical Ventilation.

Background A high number of patients with coronavirus disease 2019 (COVID-19) pneumonia who had barotrauma related to invasive mechanical ventilation at the authors' institution were observed. Purpose To determine if the rate of barotrauma in patients with COVID-19 infection was greater than in other patients requiring invasive mechanical ventilation at the authors' institution. Materials and Methods In this retrospective study, clinical and imaging data of patients seen between March 1, 2020, and April 6, 2020, who tested positive for COVID-19 and experienced barotrauma associated with invasive mechanical ventilation, were compared with patients without COVID-19 infection during the same period. Historical comparison was made to barotrauma rates of patients with acute respiratory distress syndrome from February 1, 2016, to February 1, 2020, at the authors' institution. Comparison of patient groups was performed using categoric or continuous statistical testing as appropriate, with multivariable regression analysis. Patient survival was assessed using Kaplan-Meier curves analysis. Results A total of 601 patients with COVID-19 infection underwent invasive mechanical ventilation (mean age, 63 years ± 15 [standard deviation]; 71% men). Of the total, there were 89 (15%) patients with one or more barotrauma events for a total of 145 barotrauma events (24% overall events) (95% confidence interval [CI]: 21%, 28%). During the same period, 196 patients without COVID-19 infection (mean age, 64 years ± 19; 52% men) with invasive mechanical ventilation had one barotrauma event (0.5%; 95% CI: 0%, 3%; P < .001 vs the group with COVID-19 infection). Of 285 patients with acute respiratory distress syndrome on invasive mechanical ventilation during the previous 4 years (mean age, 68 years ± 17; 60% men), 28 patients (10%) had 31 barotrauma events, with an overall barotrauma rate of 11% (95% CI: 8%, 15%; P < .001 vs the group with COVID-19 infection). Barotrauma is an independent risk factor for death in COVID-19 (odds ratio = 2.2; P = .03) and is associated with a longer hospital stay (odds ratio = 0.92; P < .001). Conclusion Patients with coronavirus disease 2019 (COVID-19) infection and invasive mechanical ventilation had a higher rate of barotrauma than patients with acute respiratory distress syndrome and patients without COVID-19 infection. © RSNA, 2020 Online supplemental material is available for this article.

Safety and Effectiveness of Yttrium-90 Radioembolization around the Time of Immune Checkpoint Inhibitors for Unresectable Hepatic Metastases.

PURPOSE: To assess the safety and effectiveness of yttrium-90 radioembolization and checkpoint inhibitor immunotherapy within a short interval for the treatment of unresectable hepatic metastases. MATERIALS AND METHODS: This single-institution retrospective study included 22 patients (12 men; median age, 65 y ± 11) with unresectable hepatic metastases and preserved functional status (Eastern Cooperative Oncology Group performance status 0/1) who received immunotherapy and radioembolization within a 15-month period (median, 63.5 d; interquartile range, 19.7-178.2 d) from February 2013 to March 2018. Primary malignancies were uveal melanoma (12 of 22; 54.5%), soft tissue sarcoma (3; 13.6%), cutaneous melanoma (3; 14%), and others (4; 18.2%). Studies were reviewed to March 2019 to assess Common Terminology Criteria for Adverse Events grade 3/4 toxicities, disease progression, and death. RESULTS: There were no grade 4 toxicities within 6 mo of radioembolization. Grade 3 hepatobiliary toxicities occurred in 3 patients (13.6%) within 6 months, 2 from rapid disease progression and 1 from a biliary stricture. Two patients (9.1%) experienced clinical toxicities, including grade 4 colitis at 6 months and hepatic abscess at 3 months. Median overall survival (OS) from first radioembolization was 20 mo (95% confidence interval [CI], 12.5-27.5 mo), and median OS from first immunotherapy was 23 months (95% CI, 15.9-30.1 mo). Within the uveal melanoma subgroup, the median OS from first radioembolization was 17.0 months (95% CI, 14.2-19.8 mo). Median time to progression was 7.8 months (95% CI, 3.3-12.2 mo), and median progression-free survival was 7.8 mo (95% CI, 3.1-12.4 mo). CONCLUSIONS: Checkpoint immunotherapy around the time of radioembolization is safe, with a low incidence of toxicity independent of primary malignancy.

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS: The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS: Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth.

We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for the establishment of tuberculous persistence. Here, yeast two-hybrid and affinity chromatography experiments have demonstrated that Rv2623 interacts with one of the two forkhead-associated domains (FHA I) of Rv1747, a putative ATP-binding cassette transporter annotated to export lipooligosaccharides. FHA domains are signaling protein modules that mediate protein-protein interactions to modulate a wide variety of biological processes via binding to conserved phosphorylated threonine (pT)-containing oligopeptides of the interactors. Biochemical, immunochemical and mass spectrometric studies have shown that Rv2623 harbors pT and specifically identified threonine 237 as a phosphorylated residue. Relative to wild-type Rv2623 (Rv2623WT), a mutant protein in which T237 has been replaced with a non-phosphorylatable alanine (Rv2623T237A) exhibits decreased interaction with the Rv1747 FHA I domain and diminished growth-regulatory capacity. Interestingly, compared to WT bacilli, an M. tuberculosis Rv2623 null mutant (ΔRv2623) displays enhanced expression of phosphatidyl-myo-inositol mannosides (PIMs), while the ΔRv1747 mutant expresses decreased levels of PIMs. Animal studies have previously shown that ΔRv2623 is hypervirulent, while ΔRv1747 is growth-attenuated. Collectively, these data have provided evidence that Rv2623 interacts with Rv1747 to regulate mycobacterial growth; and this interaction is mediated via the recognition of the conserved Rv2623 pT237-containing FHA-binding motif by the Rv1747 FHA I domain. The divergent aberrant PIM profiles and the opposing in vivo growth phenotypes of ΔRv2623 and ΔRv1747, together with the annotated lipooligosaccharide exporter function of Rv1747, suggest that Rv2623 interacts with Rv1747 to modulate mycobacterial growth by negatively regulating the activity of Rv1747; and that Rv1747 might function as a transporter of PIMs. Because these glycolipids are major mycobacterial cell envelope components that can impact on the immune response, our findings raise the possibility that Rv2623 may regulate bacterial growth, virulence, and entry into persistence, at least in part, by modulating the levels of bacillary PIM expression, perhaps through negatively regulating the Rv1747-dependent export of the immunomodulatory PIMs to alter host-pathogen interaction, thereby influencing the fate of M. tuberculosis in vivo.

Intraperitoneal Urinary Bladder Perforation with Pneumoperitoneum in Association with Indwelling Foley Catheter Diagnosed in Emergency Department.

BACKGROUND: Indwelling Foley catheter is a rare cause of urinary bladder perforation, a serious injury with high mortality that demands accurate and prompt diagnosis. While the gold standard for diagnosis of bladder injury is computed tomography (CT) cystography, few bladder ruptures associated with Foley catheter have been reported to be diagnosed in the emergency department (ED). CASE REPORT: An 83-year-old man with indwelling Foley catheter presented to the ED for hematuria and altered mental status. He was diagnosed to have intraperitoneal rupture of the urinary bladder in the ED using abdominal and pelvic CT without contrast, which demonstrated bladder wall discontinuity, intraperitoneal free fluid, and pneumoperitoneum. The patient was treated successfully with medical management and bladder drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first report of intraperitoneal urinary bladder perforation associated with Foley catheter diagnosed in the ED by CT without contrast. Pneumoperitoneum found in this case was a clue to the diagnosis and is a benign finding that does not necessitate urgent surgical intervention. The early and accurate diagnosis in this case allowed for effective management with good clinical outcome. The use of indwelling Foley catheter has a high prevalence, especially in long-term care facility residents, who are frequent visitors in the ED. Therefore, emergency physicians and radiologists should be familiar with the presentation and imaging findings of this potential injury associated with Foley catheters.

Inhibition and structure of Toxoplasma gondii purine nucleoside phosphorylase.

The intracellular pathogen Toxoplasma gondii is a purine auxotroph that relies on purine salvage for proliferation. We have optimized T. gondii purine nucleoside phosphorylase (TgPNP) stability and crystallized TgPNP with phosphate and immucillin-H, a transition-state analogue that has high affinity for the enzyme. Immucillin-H bound to TgPNP with a dissociation constant of 370 pM, the highest affinity of 11 immucillins selected to probe the catalytic site. The specificity for transition-state analogues indicated an early dissociative transition state for TgPNP. Compared to Plasmodium falciparum PNP, large substituents surrounding the 5'-hydroxyl group of inhibitors demonstrate reduced capacity for TgPNP inhibition. Catalytic discrimination against large 5' groups is consistent with the inability of TgPNP to catalyze the phosphorolysis of 5'-methylthioinosine to hypoxanthine. In contrast to mammalian PNP, the 2'-hydroxyl group is crucial for inhibitor binding in the catalytic site of TgPNP. This first crystal structure of TgPNP describes the basis for discrimination against 5'-methylthioinosine and similarly 5'-hydroxy-substituted immucillins; structural differences reflect the unique adaptations of purine salvage pathways of Apicomplexa.

Direct binding of triglyceride to fat storage-inducing transmembrane proteins 1 and 2 is important for lipid droplet formation.

The process of lipid droplet (LD) formation is an evolutionarily conserved process among all eukaryotes and plays an important role in both cellular physiology and disease. Recently, fat storage-inducing transmembrane proteins 1 and 2 (FIT1/FITM1 and FIT2/FITM2) were discovered as an evolutionarily conserved family of proteins involved in fat storage. In mammals, FIT1 is expressed primarily in skeletal muscle and FIT2 is expressed primarily in adipose, raising the possibility that FIT1 and FIT2 have unique functions. These proteins are exclusively localized to the endoplasmic reticulum (ER) and mediate triglyceride-rich LD accumulation when overexpressed in cells, mouse liver, or muscle. Unlike the ER-resident diacylglycerol O-acyltransferase family of triglyceride-synthesizing enzymes, FITs do not synthesize triglyceride, but rather partition triglyceride into LDs. The mechanism by which FIT proteins mediate this process has not been determined. A simple hypothesis was tested that FIT proteins bind to triglyceride to mediate LD formation. Here, it is shown that FIT proteins purified in detergent micelles directly bind triolein with specificity and saturation-binding kinetics. A FIT2 gain-of-function mutant that formed larger LDs, FLL(157-9)AAA, showed increased binding to triolein relative to wild-type FIT2, whereas FIT1 and a FIT2 partial loss-of-function mutant, N80A, had significantly lower triolein binding and produced smaller LDs. In summary, FIT proteins are transmembrane domain-containing proteins shown to bind triglyceride. These findings indicate that FITs have a unique biochemical mechanism in mediating LD formation and implicates triglyceride binding as important for FIT-mediated LD formation.

Comparison of periprocedural and procedure room times between moderate sedation and monitored anesthesia care in interventional radiology.

Objectives: In recent years, there has been increased utilization of monitored anesthesia care (MAC) in interventional radiology (IR) departments. The purpose of this study was to compare pre-procedure bed, procedure room, and post-procedure bed times for IR procedures performed with either nurse-administered moderate sedation (MOSED) or MAC. Material and Methods: An institutional review board-approved single institution retrospective review of IR procedures between January 2010 and September 2022 was performed. Procedures performed with general anesthesia or local anesthetic only, missing time stamps, or where <50 cases were performed for both MAC and MOSED were excluded from the study. Pre-procedure bed, procedure room, post-procedure bed, and total IR encounter times were compared between MAC and MOSED using the t-test. The effect size was estimated using Cohen's d statistic. Results: 97,480 cases spanning 69 procedure codes were examined. Mean time in pre-procedure bed was 27 min longer for MAC procedures (69 vs. 42 min, P < 0.001, d = 0.95). Mean procedure room time was 11 min shorter for MAC (60 vs. 71 min, P < 0.001, d = 0.48), and mean time in post-procedure bed was 10 min longer for MAC (102 vs. 92 min, P < 0.001, d = 0.22). Total IR encounter times were on average 27 min longer for MAC cases (231 vs. 204 min, P < 0.001, d = 0.41). Conclusion: MAC improves the utilization of IR procedure rooms, but at the cost of increased patient time in the pre- and post-procedure areas.

Sequence, structure, function, immunity: structural genomics of costimulation.

SUMMARY: Costimulatory receptors and ligands trigger the signaling pathways that are responsible for modulating the strength, course, and duration of an immune response. High-resolution structures have provided invaluable mechanistic insights by defining the chemical and physical features underlying costimulatory receptor:ligand specificity, affinity, oligomeric state, and valency. Furthermore, these structures revealed general architectural features that are important for the integration of these interactions and their associated signaling pathways into overall cellular physiology. Recent technological advances in structural biology promise unprecedented opportunities for furthering our understanding of the structural features and mechanisms that govern costimulation. In this review, we highlight unique insights that have been revealed by structures of costimulatory molecules from the immunoglobulin and tumor necrosis factor superfamilies and describe a vision for future structural and mechanistic analysis of costimulation. This vision includes simple strategies for the selection of candidate molecules for structure determination and highlights the critical role of structure in the design of mutant costimulatory molecules for the generation of in vivo structure-function correlations in a mammalian model system. This integrated 'atoms-to-animals' paradigm provides a comprehensive approach for defining atomic and molecular mechanisms.

A novel greedy adaptive ant colony algorithm for shortest path of irrigation groups.

With the full-scale implementation of facility agriculture, the laying of a water distribution network (WDN) on farmland plays an important role in irrigating crops. Especially in large areas of farmland, with the parameters of moisture sensors, the staff can divide the WDN into several irrigation groups according to the soil moisture conditions in each area and irrigate them in turn, so that irrigation can be carried out quickly and efficiently while meeting the demand for irrigation. However, the efficiency of irrigation is directly related to the pipe length of each irrigation group of the WDN. Obtaining the shortest total length of irrigation groups is a path optimization problem. In this paper, a grouped irrigation path model is designed, and a new greedy adaptive ant colony algorithm (GAACO) is proposed to shorten the total length of irrigation groups. To verify the effectiveness of GAACO, we compare it with simple modified particle swarm optimization (SMPSO), chaos-directed genetic algorithms (CDGA) and self-adaptive ant colony optimization (SACO), which are currently applied to the path problem. The simulation results show that GAACO can effectively shorten the total path of the irrigation group for all cases from 30 to 100 water-demanding nodes and has the fastest convergence speed compared to SMPSO, CDGA and SACO. As a result, GAACO can be applied to the shortest pipeline path problem for irrigation of farmland groups.

Two-dimensional layered lithium lanthanum titanium oxide/graphene-like composites as electrodes for lithium-ion batteries.

Perovskite-structured (ABO3) lithium lanthanum titanate (LixLa(2-x)/3TiO3, LLTO) is widely used in all solid state lithium ion batteries due to its high ionic conductivity. In this study, a two-dimensional LLTO nanosheet/graphene (LLTO/C) nanosheet composite has been designed as an electrode material for lithium-ion batteries (LIBs). LLTO/C not only exhibits the ionic conductivity properties of perovskite-type LLTO, but the graphene between the layers of LLTO nanosheets also endows the material with additional electronic conductivity. Moreover, LLTO@C-600 exhibits an excellent rate capability as the electrode for delithiation with a high specific capacity of 350 mA h g-1 at 20 mA g-1, and 70% of the specific capacity can be maintained at 1.0 A g-1 after 800 cycles. The excellent electrochemical performances can be attributed to the superior interficial capacitive Li+ storage capability.

Rapid Electrochemical Activation of V2 O3 @C Cathode for High-Performance Zinc-Ion Batteries in Water-in-Salt Electrolyte.

Aqueous Zn-ion batteries (ZIBs), with the advantages of low cost, high safety, and high capacity, have great potential for application in grid energy storage and wearable flexible devices. However, their commercial application is still restricted by their inferior long-term cycling stability, Zn dendrite formation, and the decomposition of aqueous electrolyte. In this study, a Zn|Zn(CF3 SO3 )2 +LiTFSI|V2 O3 @C cell is constructed to address the above issues. The V2 O3 @C electrode can be fully oxidized into amorphous V2 O5 @C simultaneously with Zn2+ and H2 O co-insertion. The cell delivers a high specific capacity of more than 240 mAh g-1 at 3 A g-1 , with extraordinary coulombic efficiency and capacity retention. The excellent electrochemical performances are attributed to synergistic effects between the V2 O3 @C electrode and the water-in-salt electrolyte with enhanced stability and improved interface reaction kinetics. Systematic improvements of this architecture indicate much promise for application.

Incorporation of a Social Virtual Reality Platform into the Residency Recruitment Season.

RATIONALE AND OBJECTIVES: The Covid-19 pandemic ushered a sudden need for residency programs to develop innovative socially distant and remote approaches to effectively promote their program. Here we describe our experience using the social virtual reality (VR) platform Mozilla Hubs for the pre-interview social during the 2020-2021 radiology residency virtual recruitment season, provide results of a survey sent to assess applicants' attitudes towards the VR pre-interview social, and outline additional use-cases for the emerging technology. MATERIALS AND METHODS: A VR Meeting Hall dedicated to the pre-interview social was designed in Mozilla Hubs. To assess applicants' impressions of the Mozilla Hubs pre-interview social, applicants were sent an optional web-based survey. Survey respondents were asked to respond to a series of eleven statements using a five-point Likert scale of perceived agreement: Strongly Agree, Agree, Neutral, Disagree, Strongly Disagree. Statements were designed to gauge applicants' attitudes towards the Mozilla Hubs pre-interview social and its usefulness in helping them learn about the residency program, particularly in comparison with pre-interview socials held on conventional video conferencing software (CVCS). RESULTS: Of the 120 residency applicants invited to the Mozilla Hubs pre-interview social, 111 (93%) attended. Of these, 68 (61%) participated in the anonymous survey. Most applicants reported a better overall experience with Mozilla Hubs compared to CVCS (47/68, 69%), with 10% (7/68) reporting a worse overall experience, and 21% (14/68) neutral. Most applicants reported the Mozilla Hubs pre-interview social allowed them to better assess residency culture than did pre-interview socials using CVCS (41/68, 60%). Seventy-two percent of applicants reported that the Mozilla Hubs pre-interview social positively impacted their decision to strongly consider the residency program (49/68). CONCLUSION: Radiology residency applicants overall preferred a pre-interview social hosted on a social VR platform, Mozilla Hubs, compared to those hosted on CVCS. Applicants reported the use of a social VR platform reflected positively on the residency and positively impacted their decision to strongly consider the program.

MRI-Derived Sarcopenia Associated with Increased Mortality Following Yttrium-90 Radioembolization of Hepatocellular Carcinoma.

PURPOSE: To evaluate the influence of sarcopenia on survival in patients with hepatocellular carcinoma (HCC) treated with 90Y radioembolization. MATERIALS AND METHODS: This single-center retrospective cohort study analyzed 82 consecutive patients (65 men and 17 women, mean age 65 years, range 31-83 years) with HCC treated with 90Y radioembolization between December 2013 and December 2017. Sarcopenia was assessed on pre-procedure MRI performed within 100 days prior to 90Y radioembolization by segmenting the paraspinal musculature at the level of the superior mesenteric artery origin and subtracting fat-intensity pixels to yield fat-free muscle area (FFMA). Sarcopenia was defined as FFMA ≤31.97 cm2 for men and ≤28.95 cm2 for women. Survival at 90 days, 180 days, 1 year, and 3 years following initial treatment was assessed using medical and public obituary records. RESULTS: Sarcopenia was identified in 30% (25/82) of patients. Death was reported for 49% (32/65) of males and 71% (8/17) of females (mean follow-up 19.6 months, range 21 days-58 months). Patients with sarcopenia were found to have increased mortality at 180 days (31.8% vs. 8.9%) and 1 year (68.2% vs. 21.2%). Sarcopenia was an independent predictor of mortality adjusted for BCLC stage and sub-analysis demonstrated that sarcopenia independently predicted increased mortality for patients with BCLC stage B disease. CONCLUSION: Sarcopenia was associated with increased 180-day and 1-year mortality in HCC patients undergoing 90Y radioembolization. Sarcopenia was an independent predictor of survival adjusted for BCLC stage with significant deviation in the survival curves of BCLC stage B patients with and without sarcopenia.

Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment.

BACKGROUND: There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. METHODS: This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6-9 months) and late follow-up (9-16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. RESULTS: The overall portomesenteric thrombosis burden improved in eight (72%) TIPS patients, three (27%) anticoagulated patients, and two (10%) untreated patients at early follow-up (p = 0.001) and in seven (78%) TIPS patients, two (29%) anticoagulated patients, and three (17%) untreated patients in late follow-up (p = 0.007). No bleeding complications attributable to anticoagulation were observed. CONCLUSION: TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.

Response assessment of hepatocellular carcinoma treated with yttrium-90 radioembolization: inter-reader variability, comparison with 3D quantitative approach, and role in the prediction of clinical outcomes.

OBJECTIVES: To assess the inter-reader variability in response assessment for HCC treated with radioembolization (TARE) compared with 3D quantitative criteria (qEASL); and to evaluate their role in prediction of pathological necrosis and clinical outcomes. MATERIALS AND METHODS: 57 patients with 77 HCCs who underwent TARE were included. Five radiologists recorded multiple imaging features and assigned mRECIST/LIRADS Treatment Response (TR) categories on post-treatment MRI at 4-6 weeks and 6-9 months after TARE. qEASL categories were assigned by a separate reader. Inter-reader variability between LIRADS TR/mRECIST/qEASL were evaluated and hazards regression was used in predicting clinical outcomes. RESULTS: Inter-reader agreement was fair for mRECIST (K = 0.43 and 0.34 at first and second follow-up respectively); moderate for LIRADS TR (K = 0.48 and 0.53 at first and second follow-up respectively). Inter-criterion agreement was moderate to substantial (r = 0.41-0.65 and r = 0.54-0.60 at first and second follow-up) for mRECIST-qEASL. LIRADS TR correlated well with qEASL for all readers at both follow-ups (K = 0.45-0.78; K = 0.39-0.77 for first and second follow-up). qEASL was the most accurate in predicting Tumor-Free Survival (TFS) on first (HR 2.23 [1.44-3.46], p < 0.001) and second (HR 1.69 [1.15-2.48], p = 0.008) follow-up. LIRADS TR was the most accurate in predicting histopathological necrosis (8 patients underwent liver transplantation and 1 patient underwent tumor resection during the period of the study). CONCLUSIONS: HCC response assessment following TARE is challenging, resulting in poor to moderate inter-reader agreement for mRECIST, and moderate inter-reader agreement for LIRADS TR response assessment criteria. qEASL outperformed mRECIST criteria for early identification of responders and predicting TFS, suggesting an advantage in volumetric tumor response assessment. LIRADS TR outperformed other criteria in predicting pathological necrosis.

Biochemical and structural characterization of the human TL1A ectodomain.

TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 A, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3 differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors.

Detection of hepatic steatosis and iron content at 3 Tesla: comparison of two-point Dixon, quantitative multi-echo Dixon, and MR spectroscopy.

PURPOSE: To compare qualitative results obtained from computer-aided dual-ratio analysis on T1-weighted two-point Dixon, with T2*-corrected multi-echo Dixon and T2-corrected multi-echo single-voxel MR spectroscopy sequence (MRS) for evaluation of liver fat and iron at 3T. METHODS AND MATERIALS: This retrospective, HIPAA-compliant, IRB-approved study included 479 patients with known or suspected liver disease. Two-point Dixon, multi-echo Dixon, and MR spectroscopy sequences were performed for each patient at 3T. A receiver-operating characteristic analysis was performed to compare the diagnostic performance in 80 patients using biopsy as the standard. Sensitivity, specificity, PPV, and NPV of qualitative two-point Dixon results, multi-echo Dixon (PDFF and R2*), and MRS (fat fraction and R2 water) for detection of hepatic steatosis and siderosis were assessed. RESULTS: Fat fractions obtained from MRS and multi-echo Dixon have equivalent accuracy for detection of hepatic steatosis (AUC, sensitivity and specificity: 0.90 vs 0.88, 0.77 vs. 0.82, and 0.90 vs. 0.82), but the optimal cutoff value is higher for MRS (6.05% vs. 3.4%). The dual-ratio Dixon discrimination technique showed high negative predictive value for detection of hepatic steatosis and siderosis (0.90 and 0.94, respectively). R2* from multi-echo Dixon and R2water from MRS have equivalent accuracy for detection of iron overload at 3T (AUC 0.89 vs. 0.88). The optimal cutoff for R2* and R2water are 60.5 s-1 and 40.85 s-1, respectively. CONCLUSION: The computer-aided dual-ratio discrimination with two-point Dixon is a useful qualitative screening tool with high negative predictive value for hepatic steatosis and iron overload. Multi-echo Dixon and MRS have similar accuracy for detection of hepatic steatosis and iron overload at 3 Tesla.

MR elastography of liver at 3 Tesla: comparison of gradient-recalled echo (GRE) and spin-echo (SE) echo-planar imaging (EPI) sequences and agreement across stiffness measurements.

PURPOSE: To compare 2D gradient-recalled echo (GRE) and 2D spin-echo (SE) echo-planar imaging (EPI) MR elastography (MRE) for measurement of hepatic stiffness in adult patients with known or suspected liver disease at 3 Tesla. MATERIALS AND METHODS: Three hundred and eighty-seven consecutive patients underwent MRE of the liver at 3 Tesla with 2D-GRE and 2D-SE-EPI sequences. 'Mean liver stiffness (LS)' calculated by averaging 3 ROIs in the right lobe, 'Maximum LS' calculated by an ROI in the right lobe; and 'Freehand LS' calculated by an ROI in the entire liver were measured by two independent readers. Inter-observer and inter-class variability in stiffness measurements were assessed. Stiffness values were correlated with degree of liver fibrosis (METAVIR scores) in 97 patients who underwent biopsy. The diagnostic performance was compared by a receiver-operating characteristic analysis. RESULTS: The technical failure rate was 2.8% for 2D-SE-EPI (11/387) and 4.1% for 2D-GRE (16/387, 9 had R2* > 80 s-1 indicating iron overload). There is high reproducibility for both GRE and SE-EPI variants (ICC = 0.84-0.94 for both GRE and SE-EPI MRE). The highest sensitivity, specificity, and accuracy of differentiating mild fibrosis (F0-F2) from advanced fibrosis (F3-F4) are 0.84 (GRE Freehand measurement), 0.92 (GRE Maximum stiffness measurement), and 0.88 (GRE Freehand measurement), respectively. CONCLUSIONS: High intra-class correlation and intra-reader correlation are seen on measured hepatic stiffness for both 2D-GRE and 2D-SE-EPI MRE. 2D-SE-EPI has lower failure rate. Diagnostic performance of both sequences is equivalent, with highest sensitivity for 2D-GRE Freehand stiffness measurement, and highest specificity 2D-GRE Maximum stiffness measurement.

Monocrystalline platinum-nickel branched nanocages with enhanced catalytic performance towards the hydrogen evolution reaction.

Single crystalline noble metal nanocages are the most promising candidates for heterogeneous catalysis due to their large specific surface area, well-defined structure and enhanced structural stability. Herein, based on the observation of an unexpected phenomenon that the alloying of Pt and transition metals by co-reduction is more preferential than the formation of pure Pt NCs, we propose a feasible one-pot strategy to synthesize a uniformly epitaxial core-shell Pt-Ni structure with a Ni-rich alloy as the core and a Pt-rich alloy as the shell. The as-prepared Pt-Ni core-shell structures are subsequently etched into monocrystalline Pt-Ni branched nanocages with the wall thickness being 2.8 nm. This unique structure exhibits excellent catalytic performance and stability for the hydrogen evolution reaction (HER) in alkaline solution which is of great significance for the energy-intensive water-alkali and chlor-alkali industry.